Flavonoids and Their Anti-Diabetic Effects: Cellular Mechanisms and Effects to Improve Blood Sugar Levels

Abstract

Diabetes mellitus (DM) is a prevailing global health metabolic disorder, with an alarming incidence rate and a huge burden on health care providers. DM is characterized by the elevation of blood glucose due either to a defect in insulin synthesis, secretion, binding to receptor, or an increase of insulin resistance. The internal and external factors such as obesity, urbanizations, and genetic mutations could increase the risk of developing DM. Flavonoids are phenolic compounds existing as secondary metabolites in fruits and vegetables as well as fungi. Their structure consists of 15 carbon skeletons and two aromatic rings (A and B) connected by three carbon chains. Flavonoids are furtherly classified into 6 subclasses: flavonols, flavones, flavanones, isoflavones, flavanols, and anthocyanidins. Naturally occurring flavonoids possess anti-diabetic effects. As in vitro and animal model’s studies demonstrate, they have the ability to prevent diabetes and its complications. The aim of this review is to summarize the current knowledge addressing the antidiabetic effects of dietary flavonoids and their underlying molecular mechanisms on selected pathways: Glucose transporter, hepatic enzymes, tyrosine kinase inhibitor, AMPK, PPAR, and NF-κB. Flavonoids improve the pathogenesis of diabetes and its complications through the regulation of glucose metabolism, hepatic enzymes activities, and a lipid profile. Most studies illustrate a positive role of specific dietary flavonoids on diabetes, but the mechanisms of action and the side effects need more clarification. Overall, more research is needed to provide a better understanding of the mechanisms of diabetes treatment using flavonoids.

Mediterranean Diet Nutrients to Turn the Tide against Insulin Resistance and Related Diseases

“…Dietary flavonoids represent a large and heterogeneous group of polyphenols ubiquitously found in daily consumed fruits and wine, as well as vegetables, nuts, cocoa, tea and grain seeds [57]. On the basis of their chemical structure, flavonoids can be categorized as flavonols, flavones, flavan-3-ols, anthocyanins, flavanones, and isoflavones [57].…”

“…Dietary flavonoids represent a large and heterogeneous group of polyphenols ubiquitously found in daily consumed fruits and wine, as well as vegetables, nuts, cocoa, tea and grain seeds [57]. On the basis of their chemical structure, flavonoids can be categorized as flavonols, flavones, flavan-3-ols, anthocyanins, flavanones, and isoflavones [57]. Recently, a meta-analysis of 8 prospective cohort studies, including a total of 312,015 participants, of whom 19,953 developed T2D during 4-28 years of follow-up, investigated the role of regular consumption of flavonoids in the prevention of diabetes, taking into account age, sex, total energy intake, body mass index (BMI), smoking, alcohol intake, and physical activity [58].…”

“…With regard to flavonoid subclasses, a beneficial effect in reducing the risk of T2D was significant for anthocyanidins, flavan-3-ols, flavonols, and isoflavones, but not for other subclasses, suggesting that different bioactive molecular pathways may be triggered by these nutrient compounds in relation to their chemical structure. By way of illustration of their speculated pharmacological antidiabetic mechanisms, we propose the lead berries-extracted quercetin, which acts as the base for the formation of other flavonol skeletons [57]. Similar to resveratrol, other flavonoids and the biguanide metformin that is recommended as the first-line intervention for diabetes treatment and prevention, quercetin can activate the insulin-independent 5 adenosine monophosphate-activated protein kinase (AMPK) pathway of skeletal muscle cells, slowing the oxygen consumption of adenosine diphosphate in isolated mitochondria [59].…”

Interaction of Catechins with Human Erythrocytes

“…Numerous beneficial health effects of catechins have been demonstrated. These compounds have been claimed to reduce cardiovascular disease mortality by inhibiting endothelial dysfunction [9], to disrupt inflammation mediated by lipid and cholesterol oxidation [10], prevent onset and complications of diabetes [11], as well as prevent and slow down the development of metabolic syndrome [12]. They are thought to exert renoprotective actions that may be of importance in diseases, such as glomerulonephritis, diabetic nephropathy, and chemically-induced kidney insufficiency [13], have antihypertensive and neuroprotective actions [14] and improve exercise performance and recovery [15].…”

The Coming Age of Flavonoids in the Treatment of Diabetic Complications

“…For this reason, there is much interest in these compounds as potential anti-diabetic drugs. This is reflected in the large number of in vitro and in vivo studies carried out to assess the effect of flavonoids in the context of diabetes [48][49][50].…”